Does clonidine (antihypertensive medication) cause bradycardia (abnormally slow heart rate)?

From the Guidelines

Clonidine can cause bradycardia as a side effect, as evidenced by the 2019 clinical practice guideline for the diagnosis, evaluation, and treatment of attention-deficit/hyperactivity disorder in children and adolescents 1. The mechanism of clonidine, an alpha-2 adrenergic agonist, reduces sympathetic outflow from the central nervous system, which decreases heart rate, blood pressure, and peripheral vascular resistance, explaining the occurrence of bradycardia in some patients. Some key points to consider:

• The risk of bradycardia is dose-dependent and more common at higher doses.
• Patients with pre-existing heart conditions, elderly individuals, and those taking other medications that slow heart rate are at increased risk.
• Bradycardia typically develops gradually after starting clonidine and may become more pronounced with continued use.
• Patients should be monitored for symptoms such as dizziness, fatigue, weakness, or syncope, which could indicate significant bradycardia requiring medical attention or dosage adjustment, as noted in the study by Wolraich et al. 1. The study also highlights the importance of monitoring vital signs in patients receiving clonidine treatment, particularly those with a history of cardiac symptoms or family history of sudden death, cardiovascular symptoms, Wolff-Parkinson-White syndrome, hypertrophic cardiomyopathy, and long QT syndrome 1. In terms of management, it is recommended to taper off clonidine rather than suddenly discontinuing it to avoid rebound hypertension, as mentioned in the 2019 guideline 1. Overall, the evidence suggests that clonidine can cause bradycardia, and patients should be closely monitored for this potential side effect, especially those at higher risk.

From the FDA Drug Label

CLINICAL PHARMACOLOGY Clonidine stimulates alpha-adrenoreceptors in the brain stem. This action results in reduced sympathetic outflow from the central nervous system and in decreases in peripheral resistance, renal vascular resistance, heart rate, and blood pressure. Slowing of the pulse rate has been observed in most patients given clonidine, but the drug does not alter normal hemodynamic response to exercise. There are post-marketing reports of patients with conduction abnormalities and/or taking other sympatholytic drugs who developed severe bradycardia requiring IV atropine, IV isoproterenol and temporary cardiac pacing while taking clonidine. Monitor heart rate in patients receiving clonidine concomitantly with agents known to affect sinus node function or AV nodal conduction, e.g., digitalis, calcium channel blockers, and beta-blockers. Sinus bradycardia resulting in hospitalization and pacemaker insertion has been reported in association with the use of clonidine concomitantly with diltiazem or verapamil. OVERDOSAGE ...hypertension may develop early and may be followed by hypotension, bradycardia, respiratory depression, hypothermia, drowsiness, decreased or absent reflexes, weakness, irritability and miosis.

Bradycardia is a potential effect of clonidine, as it slows the pulse rate in most patients. Additionally, there are reports of severe bradycardia in patients taking clonidine, especially when combined with other medications that affect heart rate.

• Key points:
  • Clonidine decreases heart rate
  • Slowing of the pulse rate is common in patients taking clonidine
  • Severe bradycardia has been reported, especially with concomitant use of other sympatholytic drugs
  • Monitoring of heart rate is recommended when clonidine is used with other medications that affect sinus node function or AV nodal conduction 2, 2, 2

From the Research

Clonidine and Bradycardia

• Clonidine, an antihypertensive medication, has been associated with bradycardia (abnormally slow heart rate) in several studies 3, 4, 5, 6.
• A study published in 1988 identified eight hypertensive patients who developed severe bradycardia during oral clonidine therapy, with seven patients having sinus bradycardia and four having long sinus pauses 3.
• Another study published in 1991 found that oral clonidine blunted the heart rate response to intravenous atropine in humans, suggesting that clonidine may cause bradycardia that is not easily reversible with atropine 4.
• A 1998 study found that clonidine premedication reduced the increase in heart rate after neostigmine-atropine administration, but did not cause severe bradycardia in any patients 7.
• The cardiac effects of clonidine, including a decrease in heart rate and stroke volume, were found to predominate early in treatment, but peripheral vascular resistance was usually reduced 5.
• A study published in 1976 suggested that clonidine causes bradycardia by stimulating both peripheral and central alpha-adrenoceptors, with the sympathetic trunk being the main pathway 6.

Risk Factors and Complications

• Patients with renal insufficiency, clinical sinus node dysfunction, and those who have developed bradycardia while taking other sympatholytic agents or are currently receiving another sympatholytic drug are at risk for severe bradycardia during oral clonidine therapy 3.
• Clonidine-induced bradycardia can be asymptomatic or symptomatic, and treatment may involve dose reduction or discontinuation of clonidine therapy, or administration of intravenous atropine sulfate or isoproterenol 3.
• The incidence of clonidine-induced bradycardia is low (less than 0.3%), but attention to risk factors can help make it even less frequent 3.